American Board of Psychiatry and Neurology (ABPN) Practice Exam

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Which medication is most likely to cause parkinsonian symptoms?

  1. Maprotiline

  2. Amoxapine

  3. Venlafaxine

  4. Doxepin

The correct answer is: Amoxapine

Amoxapine is known to potentially cause parkinsonian symptoms due to its structural similarity to typical antipsychotic medications. It has been associated with dopamine receptor antagonism, particularly D2 receptors, leading to the development of extrapyramidal side effects, which include symptoms characteristic of Parkinson's disease, such as bradykinesia, tremor, and rigidity. This effect is most commonly observed at higher doses and is a well-documented concern in the pharmacological profile of amoxapine. In contrast, the other medications listed do not share the same propensity to induce parkinsonian symptoms. Maprotiline, primarily a norepinephrine reuptake inhibitor, does not typically interfere with dopaminergic pathways in a way that would promote these side effects. Venlafaxine, an serotonin-norepinephrine reuptake inhibitor (SNRI), also lacks significant dopaminergic activity and is generally less associated with extrapyramidal symptoms. Doxepin, a tri-cyclic antidepressant, similarly does not tend to block dopamine receptors and instead acts on histamine and serotonin receptors, making parkinsonian symptoms unlikely with its use.